Tetracyclines and Glycylcyclines

Extended Spectrum Protein Synthesis Inhibitors

Tetracyclines (such as doxycycline) and glycylcyclines (such as tigecycline) act by blocking the bacterial ribosome. Tigecycline excels at bypassing common active flow pumps.

Mechanism

💊 Generic and Commercial Names

Tetracyclines: doxycycline (Vibracina), minocycline (Minocin). Glycylcyclines: tigecycline (Tygacil).

🔬 Pharmacological Group

Tetracyclines and glycylcyclines. Inhibitors of protein translation by blockade of the 30S subunit.

Mechanism of Action

Its target blocks access by the tRNA carriers:

Reversible Binding to the 30S Ribosomal Subunit: They bind reversibly to the 16S ribosomal RNA of the 30S subunit, physically blocking the access of the aminoacyl-tRNA to the acceptor site (Site A) of the ribosome-mRNA complex. By preventing this union, cellular protein elongation is interrupted in a bacteriostatic manner.
How Tigecycline Evades Resistance: Tigecycline is a derivative of minocycline that incorporates a ticeylglycylamide group at position 9. This bulky residue prevents its expulsion through the active efflux pumps of common Gram-negative bacteria and prevents target blockade mediated by common bacterial ribosomal protection proteins, restoring potency against multidrug-resistant strains.

Pharmacokinetics

Key Pharmacokinetics

Parameter	Doxycycline	Tigecycline
Routes of Administration	Oral and slow IV (minimum of 60 minutes).	Exclusively slow IV (minimum of 30-60 minutes).
Dural absorption	Excellent oral bioavailability (~95%); powerful chelator in the presence of dairy cations (Ca²⁺, Mg²⁺).	Exclusively IV.
Volume of Distribution (V_d)	High (1.5 - 2.0 L/kg). Excellent penetration into fatty tissues, prostate and saliva.	Extremely high (~7-10 L/kg). It accumulates rapidly in the intracellular compartment of peripheral tissues; very low plasma concentrations.
Protein Binding	Very high (~80-90%).	Moderately high (~70-90%).
Excretion and Half-Life	Majority mixed fecal and biliary excretion; insignificant urinary. Long half-life: 16.0 to 22.0 hours.	Majority unchanged biliary and fecal excretion (60%). Biphasic elimination half-life of 42 hours.

Antimicrobial Spectrum

Doxycycline: Excellent against atypical microorganisms, rickettsiae, spirochetes, Vibrio cholerae, Borrelia burgdorferi (Lyme) and community MRSA.
Tigecycline: Extremely broad spectrum. It covers Gram-positives (MRSA, VRE), anaerobes of all types and multidrug-resistant Gram-negatives (ESBL, AmpC, KPC). Does not innately cover Pseudomonas aeruginosa, Proteus spp. or Providencia spp.

Indicators and dose

Dosage and Adjustment

Doxycycline: 100 mg every 12 hours orally or IV. No adjustment required in renal failure.
Tigecycline: Loading dose of 100 mg IV, followed by 50 mg every 12 hours IV as a 1-hour infusion.
Adjustment of Tigecycline in Liver Failure: In severe liver failure (Child-Pugh C) the maintenance dose should be reduced to 25 mg every 12 hours after the loading dose.

Security

Contraindications and ADRs

Contraindications: Children under 8 years of age; second and third trimester of pregnancy; severe liver failure.
Adverse Effects (ADR):
- Dental and Bone Toxicity: Tetracyclines are powerful calcium chelators. They are actively deposited in the forming tooth enamel and in the developing fetal bone matrix, causing permanent yellowish-brown discoloration of the teeth and inducing enamel hypoplasia, in addition to retarding the linear growth of long bones.
- Gastrointestinal disorders (Very common with Tigecycline): Intense nausea and food intolerance in 30% of patients.
- Benign Intracranial Hypertension: Intense reversible headache and papilledema due to alteration in CSF reabsorption in the arachnoid villi.

Risk of Failure in Bacteremia due to Tigecycline

Due to its extraordinary intracellular and deep peripheral tissue distribution, the volume of distribution (V_d) of tigecycline is enormous and its free plasma levels circulating in the blood at steady state are extremely low and insufficient (dural MIC unattainable in serum). Therefore, tigecycline is relatively contraindicated and should not be used in the management of primary bacteremia, bacterial endocarditis or sepsis of urinary origin, being reserved for intra-abdominal or deep soft tissue infections.

Epistemis is educational review material. It is not a medical device, does not diagnose or prescribe treatment, and does not replace formal medical training, current clinical guidelines, or professional clinical judgment.

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System: Antimicrobial and Infectious
Group: Extended Spectrum Protein Synthesis Inhibitors

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